-Kidney is a major regulator for potassium balance. Potassium regulation -Kidney is a major regulator for potassium balance.

K+ - Reabsorption Potassium concentration in the plasma equals 4mEq/L (3.5-5.5 mEq/l ) Hyperkalemia >5.5 Hypokalemia <3.5 When K+ reaches 7-8mEq\L plus ECG changes → top emergency that requires dialysis (hemo-or peritoneal) K+-balance : K+ intake=K+ output= from 50-200mEqv (Avg. 100mEq/D) (92-95 mEq) are removed through the kidneys and the rest is removed by other routes Renal Failure hyperkalemia Renal Failure does not cause hypernatrimea because when Na increases H2O increases too thus Na+ remains relatively constant or slightly decreased.

K+ - Reabsorption K contributes to RMP (increase or decrease in Ko affects RMP and thus membrane excitability. ↓K+  hyperpolarization and cardiac arrest ↑K+  increased excitability and arrhythmia. “K+ Clearance” CK+= 60 mEq/L * 1 ml/min 4 mEq = 15 ml/min Which is much more than that for CNa+

Potassium regulation Potassium is found mainly as INTRACELLULAR ion in a concentration of 150 mEq\L If we want to calculate how much the total potassium inside the cell, we simply multiply 28L (the intracellular volume) by 150mEqv/l To calculate the extracellular total potassium we multiply 4mEqv\L by 14L(the extracellular volume) which is equal about 56 mEqv (generally speaking =60mEqv)

Potassium regulation In each large meal we ingest 50 mM of K+. Suppose that you ingest 50 mM of potassium in one meal, which are going to be distributed in the 14L of the ECF…this will increase plasma K+ by 3.6mEqv/L (this is above normal…this is very hypothetical). This makes potassium of extracellular concentration to reach 7.6 mM/l!! Very high and dangerous level..we cannot withstand!

Potassium regulation After the meal: K+ does not remain in the ECF. In the contrary, after each meal we push the ingested K+ inside the cell which acts as a BANK for potassium…this is the function of insulin which is secreted immediately after we start eating the meal. Note that the increase in intracellular concentration of potassium is harmless. Look at the figure next slide and notice the following: This resembles the relationship between potassium outside the cell and the resting membrane potential RMP given by Nernst’s Equation. The more the [K+]o, the less the negativity (less –ve RMP)…This affect the voltage sensitive channels…it turn the FRAP (fast response action potential) to SRAP.

-100 RPM mV [K+]o

Clinical note: A patient with Diabetic Ketoacidosis (a life-threatening complication in patients with untreated diabetes mellitus especially type 1 DM) came to your clinic with hyperkalemia, how you manage him/her? We know that deficiency of insulin will cause hyperkalemia when the body ingests a meal containing potassium. When insulin is given → hypokalmia Give K+ supplement with insulin. Management of diabetic ketoacidosis is by giving INSULIN and POTASSIUM

Potassium regulation 2) kidney management remember that clearance of potassium is about 15 ml\min (depends on the intake) Potassium is FREELY filtered. Filtered load equals 180L\day* 4 mEq/l= 720 mEq per day. Now how much is excreted?? As I mentioned earlier, 92 mEqv will be excreted by the kidney if the intake was 100 mEq So we have a reabsorption of (720-92=628 mEqv)...where does this reabsorption occurs?? a)2/3 of total filtered potassium is absorbed in proximal tubules (65%) b)25% from thick ascending part of Henle's loop

Potassium regulation note that the fraction filtered and NOT reabsorbed is 10% which equals 72 mEq….but 92 mEq must be excreted/D. …how this is reached? So the amount of potassium in the urine has 2 sources: (1) filtered NOT reabsorbed (2\3) (2) secreted (1\3) -We have a type of cells called principal cells found in late distal tubules and collecting ducts, these cells will secrete potassium by the following mechanism:

increased sodium entry into the cell across the luminal side will activate Na+-K+ pump at the basolateral side which will increase the intracellular concentration of K+ → make a driving force for K+ secretion

Potassium regulation How can we increase the K+ secretion?? By: 1)activate Na+-K+ pump 2)make more K+ channels at the luminal side 3)keep the gradient by removing the luminal K+…through increasing TF flow rate…this how diuretics work…they increase flow. These are the 3 mechanisms by which potassium secretion is affected.

Potassium regulation When you eat too much potassium, most of the urine potassium comes from secretion. The filtered not reabsorbed part is constant regardless the alteration in K+ intake. Back to our example of eating a meal containing K+ which will have a potential of increasing ECF- K+ …remember that the first mechanism was to push K+ inside the cell with the effect of insulin secretion…now is the role of the kidney!! -Increase K+ in ECF will activate Na+ -K+ pump and will activate aldosterone secretion which in turn increases potassium secretion

Potassium regulation How does aldosterone works? Simply it enhances sodium entry (reabsorption) to the principal cell initiating the steps for increasing potassium secretion as mentioned earlier.

Clinical notes: For every  in pH of 0.1 unit K 0.2 to 1.7 mEq/L. Acute Acidosis inhibit potassium secretion causing hyperkalemia H+ exchanges with K+ so hydrogen ions will enter the cell and potassium ions will exit through the basolateral membrane causing hyperkalemia. For every  in pH of 0.1 unit K 0.2 to 1.7 mEq/L.  Note that the term hyperkalemia may not mean a total increase in the K+ in the body, but it means that it will increase in the blood Chronic acidosis: we have inhibition of sodium-chloride reabsorption which will inhibit water absorption indeed…so we will have increase in flow and wash out (the same effect as diuretics) which will end up with hypokalemia Addison's disease which means insufficient amount of adrenal gland secretions including aldosterone will induce hyperkalemia

Clinical notes: Conn syndrome which is characterized by increase amount of aldosterone will cause hypertension and hypokalemia Hyperosmolirity will drive water outside the cells and that’s make the potassium concentration inside the cell higher (the cell actually will shrink), therefore, driving potassium outside the cell causing hyperkalemia For each 10 mOsm increase in osmolarity, this will make 0.4-0.8 mEq increase in extracellular potassium concentration Remember that the normal osmolarity in the plasma is 284mOsm (285-310) Epinephrine (through β-receptor) pushes potassium inside the cells, so giving beta blocker as propranolol will cause hyperkalemia. Exercise through α-receptors causes hyperkalemia. Thus, those who take beta-blockers and do severe exercise might suffer from serious hyperkalemia. Burns and cell lysis would increase Ko

Calcium Increase Ca++ Reabsorption Decrease Ca++ Reabsorption Proximal 65% Volume Contraction Volume Expansion TAL 25% PTH, Clacitonin Furosemide DCT 8% PTH VitD AVP (ADH) Alkalosis Thiazide Phosphate depletion Coll Ducts 1% Amiloride

Ca++ Homeostasis *PTH is the most important hormone for regulating Ca++ reabsorption *Most of the Ca++ is in the bone which serve as a reservoir (98%) and 2%in the plasma. Of the 2% of the plasma almost 50%bound and 50%free. We care about the free portion. The free part of which 99% is reabsorbed and 1% is excreted